Photodynamic therapy (PDT) is a ternary treatment for cancer involving three key components: a photosensitizer drug, light, and tissue oxygen. It is also being used for treatment of psoriasis and acne, among other skin growths and is an approved treatment for wet macular degeneration.
In photodynamic therapy, either a photosensitizer or the metabolic precursor of one is administered to the patient. A photosensitizer is a chemical compound that can be excited by light of a specific wavelength. This excitation uses visible or near-infrared light. The tissue to be treated is exposed to light suitable for exciting the photosensitizer. Usually, the photosensitizer is excited from a ground singlet state to an excited singlet state. It then undergoes intersystem crossing to a longer-lived excited triplet state. One of the few chemical species present in tissue with a ground triplet state is molecular oxygen. When the photosensitizer and an oxygen molecule are in close proximity, an energy transfer can take place that allows the photosensitizer to relax to its ground singlet state, and create an excited singlet state oxygen molecule. Singlet oxygen is a very aggressive chemical species and will very rapidly react with any nearby biomolecules. (The specific targets depend heavily on the photosensitizer chosen.) Ultimately, these destructive reactions will result in cell killing through apoptosis or necrosis.
Photodynamic therapy is delivered as an acute therapy comprising a single drug and light administration, or in a series of administrations over time (usually with months between PDT sessions). More recently, the concept of metronomic PDT (“mPDT”) has been introduced. In mPDT, the drug and/or light are delivered either in multiple pulses or continuously such that the ‘fractions’ overlap pharmacokinetically and photobiologically. (See, e.g., Stuart K. Bisland et al., “Metronomic photodynamic therapy: A novel approach to treating brain tumours,” Ontario Cancer Institute and Dept. of Medical Biophysics, University of Toronto, presented at the OPTO Canada meeting in Ottawa; 9 May 2002; and Stuart K. Bisland et al., “Metronomic Photodynamic Therapy as a New Paradigm for Photodynamic Therapy: Rationale and Preclinical Evaluation of Technical Feasibility for Treating Malignant Brain Tumors,” Photochemistry and Photobiology (July/August 2004), each of which is incorporated by reference in its entirety).
Despite these advances however, at least two important challenges remain in providing effective low dose therapy: (1) delivery of light to the target tissue over an extended period in a manner that provides consistent energy delivery to what can be an uneven surface contour; and (2) delivery of light to the target tissue over an extended period in a manner that will be acceptable to patients over this time.